Constant infusions of MTX into mice have been conducted in order to provide us further understanding of organ specificity with respect to rate of inhibition and rate of recovery of certain biochemical pathways and cell growth. Reversal of inhibition and selectivity of this reversal by nucleosides and folinic acid has also been investigated. Transport kinetics of MTX and thymidine in vivo in normal tissues and tumors is being studied by use of pharmacokinetic modeling. Initial investigations have begun with MTX linked to synthetic polymers. Testing of their selective toxic response in vivo is being conducted. In vitro studies with MTX resistant and sensitive tumor lines are being started. BIBLIOGRAPHIC REFERENCES: Zaharko, D. S., Fung, W. P. and Yang, K. H.: Relative Biochemical Aspects of Low and High Doses of MTX in Mice. Cancer Research. 37: vol. 37, in press, 1977. Pinedo, H. M., Zaharko, D. S., Bull, J. and Chabner, B. A.: The Relative Contribution of Drug Concentration and Duration of Exposure to Mouse Bone Marrow Toxicity during Continuous MTX Infusion. Cancer Res. 37: 445-450, Feb., 1977.